Diagnosis of disease and determination of treatment efficacy are important tools in medicine. IgE antibody production in an animal can be indicative of disease including, for example, allergy, atopic disease, hyper IgE syndrome, internal parasite infections and B cell neoplasia. In addition, detection of IgE production in an animal following a treatment is indicative of the efficacy of the treatment, such as when using treatments intended to disrupt IgE production.
Immunological stimulation can be mediated by IgE antibodies when IgE complexes with Fc epsilon receptors. Fc epsilon receptors are found on the surface of certain cell types, such as mast cells. Mast cells store biological mediators including histamine, prostaglandins and proteases. Release of these biological mediators is triggered when IgE antibodies complex with Fe epsilon receptors on the surface of a cell. Clinical symptoms result from the release of the biological mediators into the tissue of an animal.
The discovery of the present invention includes a novel equine Fc epsilon receptor (Fc.sub..di-elect cons. R) alpha chain protein and the use of such a protein to detect the presence of IgE in a putative IgE-containing composition; to identify inhibitors of biological responses mediated by an equine Fc.sub..di-elect cons. R protein; and as a therapeutic compound to prevent or treat clinical symptoms that result from equine Fc.sub..di-elect cons. R-mediated biological responses.
Prior investigators have disclosed the nucleic acid sequence for: the human Fc.sub..di-elect cons. R alpha chain (Kochan et al., Nucleic Acids Res. 16:3584, 1988; Shimizu et al., Proc. Natl. Acad. Sci. USA 85:1907-1911, 1988; and Pang et al., J. Immunol. 151:6166-6174, 1993); the human Fc.sub..di-elect cons. R beta chain (Kuster et al., J. Biol. Chem. 267:12782-12787, 1992); the human Fc.sub..di-elect cons. R gamma chain (Kuster et al., J. Biol. Chem. 265:6448-6452, 1990); and the canine Fc.sub..di-elect cons. R alpha chain (GenBank.TM. accession number D16413). Although the subunits of human Fc.sub..di-elect cons. R have been known as early as 1988, they have never been used to identify an equine Fc.sub..di-elect cons. R. Similarly, even though the canine Fc.sub..di-elect cons. R chain has been known since 1993, it has never been used to identify an equine Fc.sub..di-elect cons. R. Moreover, the determination of human and canine Fc epsilon receptor sequences does not indicate, suggest or predict the cloning of a novel Fc.sub..di-elect cons. R gene from a different species, in particular, from an equine species. Previous investigators have found a low degree of similarity between rat, mouse and human Fc.sub..di-elect cons. R.alpha. (Ravtech et al., Ann. Rev. Immunol. Vol. 9, pp. 457-492, 1991). Thus, given this low degree of sequence similarity, it would appear only "obvious to try" to obtain an equine Fc.sub..di-elect cons. R.alpha. nucleic acid molecule and protein.
Thus, products and processes of the present invention are needed in the art that will provide specific detection of IgE, in particular equine IgE, and treatment of Fc epsilon receptor-mediated disease.